The Effects of Long-term Macrolide Therapy in COPD Patients with Frequent Exacerbations

Exacerbations of chronic obstructive pulmonary disease (COPD) have a major impact on lung function, morbidity and mortality. Macrolide antibiotics have been successfully used as maintenance treatment in several chronic inflammatory pulmonary diseases. We demonstrated that a regimen of azithromycin treatment 500 mg three times a week during one year compared to placebo, leads to a larger reduction in exacerbation frequency in COPD patients with a minimum of three exacerbations in the previous year. We investigated the role of viral infections. We found a viral infection in a quarter of exacerbations. It was found that human rhinovirus (HRV) was most prevalent with a peak in July. COPD patients with frequent exacerbations showed the best response to maintenance treatment with azithromycin in patients with the following characteristics: baseline blood eosinophil count ≥ 2.0% (compared to an eosinophil count < 2.0%), GOLD stage 1-2 (versus GOLD stage 4) and GOLD group C (compared to group D). We determined the effect of azithromycin maintenance therapy on the dynamics of macrolide resistance genes in the pharyngeal microbiota. It was shown that the acquisition of macrolide resistance genes was limited but the relative abundance of macrolide resistance genes increased significantly over time compared to placebo

Development of the ProPal-COPD tool to identify patients with COPD for proactive palliative care

Contains fulltext : 176990.pdf (publisher's version ) (Open Access)BACKGROUND: Our objective was to develop a tool to identify patients with COPD for proactive palliative care. Since palliative care needs increase during the disease course of COPD, the prediction of mortality within 1 year, measured during hospitalizations for acute exacerbation COPD (AECOPD), was used as a proxy for the need of proactive palliative care. PATIENTS AND METHODS: Patients were recruited from three general hospitals in the Netherlands in 2014. Data of 11 potential predictors, a priori selected based on literature, were collected during hospitalization for AECOPD. After 1 year, the medical files were explored for the date of death. An optimal prediction model was assessed by Lasso logistic regression, with 20-fold cross-validation for optimal shrinkage. Missing data were handled using complete case analysis. RESULTS: Of 174 patients, 155 patients were included; of those 30 (19.4%) died within 1 year. The optimal prediction model was internally validated and had good discriminating power (AUC =0.82, 95% CI 0.81-0.82). This model relied on the following seven predictors: the surprise question, Medical Research Council dyspnea questionnaire (MRC dyspnea), Clinical COPD Questionnaire (CCQ), FEV1% of predicted value, body mass index, previous hospitalizations for AECOPD and specific comorbidities. To ensure minimal miss out of patients in need of proactive palliative care, we proposed a cutoff in the model that prioritized sensitivity over specificity (0.90 over 0.73, respectively). Our model (ProPal-COPD tool) was a stronger predictor of mortality within 1 year than the CODEX (comorbidity, age, obstruction, dyspnea, and previous severe exacerbations) index. CONCLUSION: The ProPal-COPD tool is a promising multivariable prediction tool to identify patients with COPD for proactive palliative care

Hypocapnia correction as a working mechanism for breathing retraining in asthma

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"Can Do" Versus "Do Do" in Patients with Asthma at First Referral to a Pulmonologist

BACKGROUND: Pharmacotherapy is key in asthma control, including preventing lung function decline, in primary care. However, patients' physical functioning (eg, physical capacity [PC] [=can do] and physical activity [PA] [=do do]) correlates poorly with lung function. Therefore, a better insight into the physical function of patients with asthma is needed, using the "can do, do do" concept. OBJECTIVE: To explore the "can do, do do" concept in adult patients with asthma at referral for the first time to an outpatient consultation of a pulmonologist. METHODS: PC was measured using the six-minute walk test and PA by using an accelerometer. Patients were classified into quadrants: low PC (6-minute walking distance RESULTS: A total of 479 patients with asthma had a median (interquartile range) 6-minute walking distance of 74% (66%82%) predicted, and walked 6829 (4593-9075) steps/d. Only 29% were classified as "can do, do do," whereas 30% were classified as "can't do, don't do." The Asthma Control Questionnaire and the Asthma Quality of Life Questionnaire scores were worst in the "can't do" groups. CONCLUSIONS: Low PC and/or PA was found in most patients with asthma at the index referral to a pulmonologist. An impaired PC is accompanied by a significantly reduced asthma control and disease-specific quality of life. This justifies further studies on safety and efficacy of nonpharmacological interventions, such as physiotherapy. (C) 2020 American Academy of Allergy, Asthma & Immunolog

"Can do" versus "do do": A Novel Concept to Better Understand Physical Functioning in Patients with Chronic Obstructive Pulmonary Disease

Contains fulltext : 203249.pdf (publisher's version ) (Open Access)10 p

Impact of Treatable Traits on Asthma Control and Quality of Life.

BACKGROUND: Many adult patients with asthma have uncontrolled disease and impaired quality of life, despite current asthma-specific drug therapies. OBJECTIVE: This study aimed to investigate the prevalence of 9 traits in patients with asthma, their associations with disease control and quality of life, and referral rates to nonmedical health care professionals. METHODS: Retrospectively, data from patients with asthma were collected in 2 Dutch hospitals (Amphia Breda and RadboudUMC Nijmegen). Adult patients without exacerbation <3 months who were referred for a first-ever elective, outpatient, hospital-based diagnostic pathway were deemed eligible. Nine traits were assessed: dyspnea, fatigue, depression, overweight, exercise intolerance, physical inactivity, smoking, hyperventilation, and frequent exacerbations. To assess the likelihood of having poor disease control or decreased quality of life, the odds ratio (OR) was calculated per trait. Referral rates were assessed by checking patients' files. RESULTS: A total of 444 adults with asthma were studied (57% women, age: 48 ± 16 years, forced expiratory volume in 1 second: 88% ± 17% predicted). Most patients (53%) were found to have uncontrolled asthma (Asthma Control Questionnaire ≥1.5 points) and decreased quality of life (Asthma Quality of Life Questionnaire <6 points). Generally, patients had 3.0 ± 1.8 traits. Severe fatigue was most prevalent (60%) and significantly increased the likelihood of having uncontrolled asthma (OR: 3.0, 95% confidence interval [CI]: 1.9-4.7) and decreased quality of life (OR: 4.6, 95% CI: 2.7-7.9). Referrals to nonmedical health care professionals were low; most referrals were to a respiratory-specialized nurse (33%). CONCLUSION: Adult patients with asthma with a first-ever referral to a pulmonologist frequently exhibit traits justifying the deployment of nonpharmacological interventions, especially in those with uncontrolled asthma. However, referrals to appropriate interventions appeared infrequent

Prevalence of hyperventilation in patients with asthma

OBJECTIVE: Asthma is frequently accompanied by dysfunctional breathing of which hyperventilation has been recognized as a subtype. The prevalence of hyperventilation in stable asthma has been scantily studied using blood gas analysis. Hence, a reliable estimate of its prevalence is lacking. It is unknown whether the Nijmegen Questionnaire (NQ) is a useful screening tool for hyperventilation in asthma. Therefore, the primary aim of this study was to determine the prevalence of hyperventilation in a large sample of patients with asthma in a stable state of disease. Secondary aims were to compare the clinical characteristics between patients with and without hyperventilation, and, to examine the concurrent validity of the NQ to detect hypocapnia in patients with asthma. METHODS: A real-world, observational, multicenter study was conducted. Capillary blood gas analysis was performed in adults with a confirmed diagnosis of stable asthma. A subset of patients completed the NQ. RESULTS: A blood gas analysis was obtained in 1006 patients. In 17% of the patients an acute hyperventilation was found, and in another 23% a chronic hyperventilation was uncovered. Patients with a chronic hyperventilation blood gas were more often female, were younger and had a better spirometric outcomes. The NQ appeared not to correlate with PCO2. CONCLUSION: Hyperventilation is common in patients with stable asthma. Chronic hyperventilation is more often found in females of younger age and with the best spirometric outcomes compared to patients without hyperventilation. The NQ is not a suitable screening tool for the presence of hyperventilation in stable asthmatics

Influence of macrolide maintenance therapy and bacterial colonisation on exacerbation frequency and progression of COPD (COLUMBUS):Study protocol for a randomised controlled trial

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by progressive development of airflow limitation that is poorly reversible. Because of a poor understanding of COPD pathogenesis, treatment is mostly symptomatic and new therapeutic strategies are limited. There is a direct relationship between the severity of the disease and the intensity of the inflammatory response. Besides smoking, one of the hypotheses for the persistent airway inflammation is the presence of recurrent infections. Macrolide antibiotics have bacteriostatic as well as anti-inflammatory properties in patients with cystic fibrosis and other inflammatory pulmonary diseases. There is consistent evidence that macrolide therapy reduces infectious exacerbations, decreases the requirement for additional antibiotics and improves nutritional measures. Because of these positive effects we hypothesised that maintenance macrolide therapy may also have beneficial effects in patients with COPD who have recurrent exacerbations. The effects on development of bacterial resistance to macrolides due to this long-term treatment are unknown. Until now, studies investigating macrolide therapy in COPD are limited. The objective of this study is to assess whether maintenance treatment with macrolide antibiotics in COPD patients with three or more exacerbations in the previous year decreases the exacerbation rate in the year of treatment and to establish microbial resistance due to the long-term treatment. METHODS/DESIGN: The study is set up as a prospective randomised double-blind placebo-controlled single-centre trial. A total of 92 patients with COPD who have had at least three exacerbations of COPD in the previous year will be included. Subjects will be randomised to receive either azithromycin 500 mg three times a week or placebo. Our primary endpoint is the reduction in the number of exacerbations of COPD in the year of treatment. DISCUSSION: We investigate whether long-term therapy with macrolide antibiotics can prevent exacerbations in patients with COPD. Additionally, our study aims to assess the effect of long-term use of macrolide on the development of antimicrobial resistance and on inflammatory parameters related to COPD. We believe this study will provide more data on the effects of macrolide treatment in patients in COPD and will add more knowledge on its working mechanisms. TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT0098524

Azithromycin maintenance treatment in patients with frequent exacerbations of chronic obstructive pulmonary disease (COLUMBUS): a randomised, double-blind, placebo-controlled trial

Background Macrolide resistance is an increasing problem; there is therefore debate about when to implement maintenance treatment with macrolides in patients with chronic obstructive pulmonary disease (COPD). We aimed to investigate whether patients with COPD who had received treatment for three or more exacerbations in the previous year would have a decrease in exacerbation rate when maintenance treatment with azithromycin was added to standard care. Methods We did a randomised, double-blind, placebo-controlled, single-centre trial in the Netherlands between May 19, 2010, and June 18, 2013. Patients (>= 18 years) with a diagnosis of COPD who had received treatment for three or more exacerbations in the previous year were randomly assigned, via a computer-generated randomisation sequence with permuted block sizes of ten, to receive 500 mg azithromycin or placebo three times a week for 12 months. Randomisation was stratified by use of long-term, low-dose prednisolone (<= 10 mg daily). Patients and investigators were masked to group allocation. The primary endpoint was rate of exacerbations of COPD in the year of treatment. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00985244. Findings We randomly assigned 92 patients to the azithromycin group (n=47) or the placebo group (n=45), of whom 41 (87%) versus 36 (80%) completed the study. We recorded 84 exacerbations in patients in the azithromycin group compared with 129 in those in the placebo group. The unadjusted exacerbation rate per patient per year was 1.94 (95% CI 1.50-2.52) for the azithromycin group and 3.22 (2.62-3.97) for the placebo group. After adjustment, azithromycin resulted in a significant reduction in the exacerbation rate versus placebo (0.58, 95% CI 0.42-0.79; p=0.001). Three (6%) patients in the azithromycin group reported serious adverse events compared with five (11%) in the placebo group. During follow-up, the most common adverse event was diarrhoea in the azithromycin group (nine [19%] patients vs one [2%] in the placebo group; p=0.015). Interpretation Maintenance treatment with azithromycin significantly decreased the exacerbation rate compared with placebo and should therefore be considered for use in patients with COPD who have the frequent exacerbator phenotype and are refractory to standard care